Genetic Variant PCED1B:p.Val262Met (chr12-47235847-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_138371.3(PCED1B):c.784G>A(p.Val262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000838 in 1,574,288 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 3 hom. )

Consequence

PCED1B
NM_138371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.415

Publications

0 publications found

Variant links:

Genes affected

PCED1B (HGNC:28255): (PC-esterase domain containing 1B) This gene encodes a protein that belongs to the GDSL/SGNH-like acyl-esterase family. Members of this family are hydrolases thought to function in modification of biopolymers on the cell surface. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

PCED1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10412532).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138371.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCED1B	NM_138371.3	MANE Select	c.784G>A	p.Val262Met	missense	Exon 4 of 4	NP_612380.1	Q96HM7
	PCED1B	NM_001281429.2		c.784G>A	p.Val262Met	missense	Exon 3 of 3	NP_001268358.1	Q96HM7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCED1B	ENST00000546455.6	TSL:1 MANE Select	c.784G>A	p.Val262Met	missense	Exon 4 of 4	ENSP00000446688.1	Q96HM7
PCED1B	ENST00000432328.2	TSL:3	c.784G>A	p.Val262Met	missense	Exon 3 of 3	ENSP00000396040.1	Q96HM7
PCED1B	ENST00000872013.1		c.784G>A	p.Val262Met	missense	Exon 4 of 4	ENSP00000542072.1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.0000556

AC:

AN:

179708

AF XY:

0.0000513

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.000116

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000209

GnomAD4 exome

AF:

0.0000830

AC:

118

AN:

1422086

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

704188

show subpopulations

African (AFR)

AF:

0.0000309

AC:

AN:

32348

American (AMR)

AF:

0.000265

AC:

AN:

37736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25336

East Asian (EAS)

AF:

0.00

AC:

AN:

37274

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50222

Middle Eastern (MID)

AF:

0.00839

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000449

AC:

AN:

1092208

Other (OTH)

AF:

0.000136

AC:

AN:

58946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41536

American (AMR)

AF:

0.000392

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.000170

ExAC

AF:

0.0000168

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.38

M_CAP

Benign

0.0083

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.41

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.0

REVEL

Benign

0.086

Sift

Benign

0.064

Sift4G

Benign

0.23

Polyphen

0.99

Vest4

0.23

MVP

0.30

MPC

0.80

ClinPred

0.15

GERP RS

-0.27

Varity_R

0.042

gMVP

0.23

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over